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Metabolism and immunity have long been classified in distinct research fields; however, the concept of immunometabolism has recently highlighted their close relationship. Immune cells in an infectious context undergo a metabolic reprogramming that leads to the accumulation of metabolites. Some of these metabolites, called metabokines, play a crucial role in anti-infectious immunity by having immunoregulatory and antimicrobial defence properties. On the one hand, metabokines regulate the response of host immune cells by modulating intracellular signalling and/or inducing post-translational modifications of proteins. On the other hand, metabokines can directly or indirectly target pathogens by inhibiting microbial metabolic pathways, restoring the sensitivity of bacteria to antibiotics, and disrupting viral replication cycles. These discoveries on metabokine properties could pave the way for the development of innovative anti-infectious metabolic treatments., (© 2021 médecine/sciences – Inserm.)

Phagocytosis and macroautophagy, named here autophagy, are two essential mechanisms of lysosomal degradation of diverse cargos into membrane structures. Both mechanisms are involved in immune regulation and cell survival. However, phagocytosis triggers degradation of extracellular material whereas autophagy engulfs only cytoplasmic elements. Furthermore, activation and maturation of these two processes are different. LAP (LC3-associated phagocytosis) is a form of phagocytosis that uses components of the autophagy pathway. It can eliminate (i) pathogens, (ii) immune complexes, (iii) threatening neighbouring cells, dead or alive, and (iv) cell debris, such as POS (photoreceptor outer segment) and the midbody released at the end of mitosis. Cells have thus optimized their means of elimination of dangerous components by sharing some fundamental elements coming from the two main lysosomal degradation pathways., (© 2019 médecine/sciences – Inserm.)

The syndrome of inappropriate antidiuresis (SIAD; formerly the syndrome of inappropriate secretion of antidiuretic hormone) is the most frequent cause of hyponatremia. A strong association exists between mortality and hyponatremia, which reflects the severity of the underlying disease. In SIAD, hyponatremia is associated with normovolaemia but the assessment of extracellular volume can be difficult. Clinical features are mainly neurological and can lead to death but mechanisms of adaptation can limit cerebral oedema. The notion of mild asymptomatic hyponatremia was questioned by the observation of subclinical neurocognitive impairment, a greater risk of falls and fractures. Aetiologies are classified into six groups: neurologic disorders, infections mainly cerebral, meningeal and pulmonary, drugs in particular antidepressants, tumors, genetic causes, and idiopathic. Symptomatic acute hyponatremia is a therapeutic emergency that is not specific of SIAD. When hyponatremia is asymptomatic, fluid restriction with salt intake is generally sufficient but urea can be an alternative. In chronic SIAD, there is currently no recommendation. Fluid restriction is not always feasible; urea has proved its efficacy, its good tolerance and its long-term harmlessness. Vaptans have demonstrated their good tolerance and their efficacy on the correction of hyponatremia from SIAD in studies subgroups, for moderate hyponatremia and asymptomatic patients. In the only study having compared vaptans and urea, efficacy and tolerance were similar. Because of the cost difference between vaptans and urea and while waiting for follow-up studies, urea appears at present as the first-line treatment of hyponatremia in SIAD., (Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family that is expressed and secreted by glandular cells and found in the secondary granules of neutrophils from which it is released in infected tissues and blood during the inflammatory process. Initially described as an iron-binding molecule with bacteriostatic properties, Lf is now known to be a multifunctional or multi-tasking protein. It is a major component of the innate immune system of mammals. Its protective effects range from direct anti-microbial activities against a large panel of microorganisms including bacteria, viruses, fungi, and parasites, to anti-inflammatory and anti-cancer activities. While iron chelation is central to some of the biological functions of Lf, other activities involve interactions of Lf with molecular and cellular components of both hosts and pathogens. Its powerful antimicrobial activities, immunomodulatory properties and prevention of septic shock, anti-carcinogenic functions and its growing importance in iron delivery and bone growth, combined with the data obtained either by in vivo studies or clinical trials, make this molecule and its derivatives very promising tools for health or nutritional applications.

Decreased drug metabolism, hyperbilirubinemia and intrahepatic cholestasis are frequently observed during inflammation. Additionally, it has long been appreciated that exposure to drug metabolism-inducing xenobiotics can impair immune function. The nuclear receptor CAR (constitutive androstane receptor or NR1I3) and PXR (pregnane X receptor, NR1I2) control phase I (cytochrome P450 2B and 3A), phase II (GSTA, UGT1A1), and transporter (MDR1, SLC21A6, MRP2) genes involved in drugs metabolism, bile acids and bilirubin clearance in response to xenobiotics. It is well known that inflammation, through the activation of NF-kappaB pathway, leads to a decrease of CAR, PXR and RXRalpha expression and the expression of their target genes. In addition, a new study reveals the mutual repression between PXR and NF-kappaB signaling pathways, providing a molecular mechanism linking xenobiotic metabolism and inflammation.

The occurrence of a postoperative complication represents an additional stress factor for patients and leads in many cases rapidly to a malnutrition status. Thus a nutritional support is required as soon as the foreseeable duration of starvation has a longer duration than one week. Considering its lower risk of septic complications and lower cost, enteral feeding should be initiated as soon as possible. Appraisal of caloric needs with standard formulas often leads to inappropriate nutritional management. Therefore the requirements should be assessed by indirect calorimetry if available. Nutritional support is a part of the management of a postoperative septic patient. It must be initiated when initial phase of haemodynamic instability is amended. Branched chain amino acids, medium chain triglycerides and other specific nutrients have failed to demonstrate a real clinical beneficial effect. In case of acute respiratory failure, nutritional support must be cautious with regard to caloric load, as carbohydrates may increase CO2 production and lipids may worsen hypoxaemia. In case of postoperative acute renal failure, nutritional management is facilitated by continuous haemofiltration techniques allowing an unlimited nutrient intake. Solutions containing only essential amino acids are not recommended. During severe acute pancreatitis, enteral feeding is indicated when ileus does not permit the use of the intestinal tract. Jejunal access must be preferred to stomach or duodenum. Lipid emulsions can be used safely if serum triglyceride concentrations remain below 4 g.L-1 during infusion and below 2 g.L-1 between infusions.

Thyroxin binding prealbumin (TBPA) and retinol binding protein (RBP) are associated in a complex responsible for the transport of vitamin A and of about 10% of the thyroid hormones T3 and T4. Both are synthetized in the liver. RBP can be characterized by two essential points: its hepatic secretion depending on the nutritional vitamin A status explains the close relation noted between these two parameters; its catabolism located in the renal tubular cells indicates the important role played by kidney in its metabolism. The concentrations, in serum of normal healthy adults, of TBPA and RBP are respectively 323 mg/l and 63 mg/l for men, 283 mg/l and 52 mg/l for women. In these cases the variations of the two proteins are significantly correlated. In patients with liver diseases and with protein deficiency, there is a lack of synthesis of TBPA and RBP (deficiency in substrate and/or decrease in hepatic synthesis). In vitamin A deficiency and in renal failure, RBP alone is disturbed.

Pharmacokinetic parameters of ceftriaxone were studied on day 1 and 5 in 21 patients admitted in an ICU for severe infections. All patients received a single daily infusion of 2 g of ceftriaxone during 15 minutes. We have determined the ratio to the daily dose of serum ceftriaxone concentrations (peak level and trough level) and of areas under the curve. According to renal function and the existence of cholestasis, the results of our study showed: 1) In patients with creatinine clearance greater than 10 ml/mn and without cholestasis, a single daily infusion of 2 g ceftriaxone achieves therapeutic blood levels without any accumulation phenomenon. 2) In patients requiring hemodialysis without cholestasis, the period between two 2 g doses should be prolonged to 48 h. 3) Marked cholestasis and creatinine clearance greater than 10 ml/mn prolong the elimination half-life of ceftriaxone leading to an interval extension of the single dose of 2 g. Further investigations are needed in the latter situation.

Transferrin structure, metabolism and physiological functions (iron transport, activation of cellular growth, bacteriostatic effect) are described with reference to the last informations available from the literature. This analysis results in a better understanding of the mechanisms involved in its physiopathological variations. Decreased serum transferrin levels are the result of a reduction of the biosynthesis (hepatic deficiencies, malnutrition), or an increase of catabolism (acute, chronic and malignant infections), or an increase of intestinal or renal losses, or very infrequently genetic disorders. Increased serum transferrin levels are the result of either hyposiderosis or an oestrogenic impregnation. Alcoholism and diabetes are responsible of qualitative modifications of this protein.